|
|
GEO help: Mouse over screen elements for information. |
|
Status |
Public on Oct 16, 2023 |
Title |
Choroid plexus defects in Down syndrome brain organoids enhance neurotropism of SARS-CoV-2 |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by high throughput sequencing
|
Summary |
Why individuals with Down Syndrome (DS, trisomy 21) are particularly susceptible to SARS-CoV-2 induced disease remains largely unclear. The choroid plexus secrets the cerebrospinal fluid and strongly expresses the ACE2 receptor and the chromosome 21 encoded TMPRSS2 protease. To investigate the role of the choroid plexus in SARS-CoV-2 central nervous system infection in DS, we established a new type of brain organoid from DS and isogenic euploid control iPSC that consists of a core of appropriately patterned functional cortical neuronal cell types that is surrounded by a patent and functional choroid plexus (CPCOs). Remarkably, DS-CPCOs not only recapitulated abnormal features of DS cortical development but also revealed defects in ciliogenesis and epithelial cell polarity of the developing choroid plexus. We next demonstrate that the choroid plexus layer facilitates SARS-CoV-2 replication and infection of cortical neuronal cells, and that this is increased in DS-CPCOs. We further show that inhibition of TMPRSS2 activity in DS-CPCOs inhibits SARS-CoV-2 infectivity. We conclude that CPCOs are a useful model for dissecting the role of the choroid plexus in euploid and DS forebrain development and enables screening for therapeutics that can inhibit SARS-CoV-2 induced neuro-pathogenesis.
|
|
|
Overall design |
Comparative gene expression profiling analysis of RNA-seq data for euploid (EU79) and down syndrome (DS) brain organoids with Choroid plexus (CP) upon infection with SARS-CoV-2.
|
|
|
Contributor(s) |
Slonchak A |
Citation(s) |
38838150 |
|
Submission date |
Jul 18, 2022 |
Last update date |
Jun 26, 2024 |
Contact name |
Andrii Slonchak |
E-mail(s) |
a.slonchak@uq.edu.au
|
Phone |
61733653302
|
Organization name |
The University of Queensland
|
Department |
School Of Chemistry And Molecular Biosciences
|
Street address |
MBS Bldg 76, Cooper Rd
|
City |
St Lucia |
State/province |
QLD |
ZIP/Postal code |
4072 |
Country |
Australia |
|
|
Platforms (1) |
GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
|
Samples (12)
|
GSM6346479 |
Euploid human brain organoids, uninifected 1 |
GSM6346480 |
Euploid human brain organoids, uninifected 2 |
GSM6346481 |
Euploid human brain organoids, uninifected 3 |
GSM6346482 |
Euploid human brain organoids, 24h post SARS-CoV-2 infection 1 |
GSM6346483 |
Euploid human brain organoids, 24h post SARS-CoV-2 infection 2 |
GSM6346484 |
Euploid human brain organoids, 24h post SARS-CoV-2 infection 3 |
GSM6346485 |
Down Syndrome human brain organoids, uninfected 1 |
GSM6346486 |
Down Syndrome human brain organoids, uninfected 2 |
GSM6346487 |
Down Syndrome human brain organoids, uninfected 3 |
GSM6346488 |
Down Syndrome human brain organoids, 24h post SARS-CoV-2 infection 1 |
GSM6346489 |
Down Syndrome human brain organoids, 24h post SARS-CoV-2 infection 2 |
GSM6346490 |
Down Syndrome human brain organoids, 24h post SARS-CoV-2 infection 3 |
|
Relations |
BioProject |
PRJNA859925 |
Supplementary file |
Size |
Download |
File type/resource |
GSE208440_Count_matrix.txt.gz |
528.5 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
Raw data are available in SRA |
Processed data are available on Series record |
|
|
|
|
|